Refractory Multiple MyelomaPhase 2OptiPOMNCT03520985
Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma
A Phase 2 study testing Pomalidomide and Dexamethasone in people with Refractory Multiple Myeloma, run by Swiss Cancer Institute at 16 sites in Switzerland.
Trial summary
Pomalidomide is an approved treatment for refractory multiple myeloma. Toxicity of pomalidomide in the pivotal MM-003 trial, was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Multiple Myeloma
- What is being tested?
- Pomalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 16 sitesSwitzerland
- Study dates
- 1 Oct 2018to 3 Feb 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient was diagnosed with multiple myeloma based on standard IMWG criteria
- Prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
- Patients must have been exposed to both lenalidomide and bortezomib
- Measurable disease for myeloma defined as one of the following: serum M-protein ≥ 5 g/L; urine M-protein ≥ 0.2 g/24 hours
- Refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy.
- Adequate hematological and hepatic function
- A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential
Who cannot join
- History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration, with the exception of pT1-2 prostate cancer Gleason score ≤6, adequately treated, cervical carcinoma in situ or localized non-melanoma skin cancer.
- Polyneuropathy grade > 2
- Patients who received any of the following within the last 14 days of initiation of trial treatment:
- Plasmapheresis
- Major surgery (kyphoplasty is not considered major surgery)
- Radiation therapy
Show all 9Show fewer
- Use of any anti-myeloma drug therapy
- Known or clinically suspected myeloma manifestations in the central nervous system
- Severe or uncontrolled cardiovascular disease
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Switzerland16 sites
Kantonspital Aarau
Aarau, CH-5001
Kantonsspital Baden (Baden/Brugg)
Baden, 5404
Universitätsspital Basel
Basel, 4031
Istituto Oncologico Svizzera Italiana IOSI
Bellinzona, 6500
Inselspital Bern
Bern, 3010
Kantonsspital Graubünden
Chur, CH-7000
Hopital Fribourgeois HFR
Fribourg, 1708
Kantonsspital Liestal
Liestal, CH-4410
Kantonsspital Luzern
Luzerne, CH-6000
Spital Thurgau AG
Münsterlingen, 8596
Kantonsspital St. Gallen
Sankt Gallen, 9007
Regionalspital Thun
Thun, 3600
Kantonsspital Winterthur
Winterthur, 8401
Onkozentrum Hirslanden Zürich
Zurich, 8032
OnkoZentrum Zürich AG - Klinik im Park
Zurich, 8038
Universitätsspital Zürich
Zurich, 8091
About this study
Official title: Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial
Pomalidomide is an approved treatment for refractory multiple myeloma. Toxicity of pomalidomide in the pivotal MM-003 trial, was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule is too toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance. The aim of this trial therefore is to establish that alternate day dosing of pomalidomide (4 mg q2d, d1-28) is non-inferior to daily dosing (4 mg d1-21 q28) in terms of efficacy of the drug with potentially less side effects.
Read the detailed description
Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all hematological malignancies. Despite recent advances in myeloma treatment, including the introduction of proteasome inhibitors, immunomodulatory drugs (IMiDs) and stem cell transplantation, myeloma remains an incurable disease. The treatment of bortezomib and lenalidomide refractory myeloma is still an unmet medical need. Once patients have relapsed after IMiD-containing therapies and have become bortezomib-resistant, their prognosis is extremely poor.
Pomalidomide is a third-generation, Swissmedic approved, oral immunomodulatory drug with activity in such patients. However the toxicity of pomalidomide in the pivotal MM-003 trial was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule (4 mg daily on 21 of 28 days) is toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance.
Alternative dosing schedules:
There is robust data available indicating that lower pomalidomide doses (e.g. 2 mg daily) lead to similar responses and progression free survival with fewer side effects. Due to its unique pharmacological characteristics, pomalidomide is well suited for alternate day dosing. The decline of the plasma concentration at the terminal phase is slow. These data make pomalidomide an ideal candidate for alternate day dosing. Therefore, a phase I study has already been conducted in 2008 to test the alternating administration of the drug showing excellent responses with a marked reduction of thrombotic events and less severe myelosuppression.
The drug costs of pomalidomide are quite high. Interestingly, the manufacturer determined a pricing model that is independent from the capsule strength (costs for one capsule 1 mg=2 mg=3 mg=4 mg). In patients requiring dose reductions due to hematologic toxicity, daily dosing of reduced strength pomalidomide (e.g. 2 mg daily) is approved and suggested by the manufacturer. This delivers 50% less pomalidomide to the patient, albeit at 100% of the price of full dosing.
In summary, the establishment of the modified pomalidomide schedule would be an interesting option for our patients to achieve similar efficacy with fewer side effects. In addition, it would optimize the cost-effectiveness of the drug.
- Conditions
- Refractory Multiple Myeloma
- Being tested
- Pomalidomide, Dexamethasone
- Keywords
- refractory Multiple Myeloma, Phase II, Pomalidomide, OptiPOM
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PomalidomideDrug
Also called Imnovid®
Pomalidomide (4 mg p.o.) will be administered on every other day of each 28-day treatment cycle.
Treatment duration:
Treatment cycles are repeated until confirmed disease progression.
DexamethasoneDrug
For patients ≤ 75 years of age:
Low-Dose Dexamethasone (40 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle.
For patients > 75 years of age:
Low-Dose Dexamethasone (20 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle.
Treatment duration:
Treatment cycles are repeated until confirmed disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Pomalidomide | Experimental | The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX) Receives: Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
OR is defined as minimal response or better, assessed according to the IMWG criteria.
Measured: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
Secondary outcomes (3)
Overall Survival (OS)
OS is defined as the time from registration until death from any cause. Patients not having an event at the time of analysis will be censored at the date they were last known to be alive.
Measured: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
Overall Survival (OS) at 12 months
OS, as defined above, will be evaluated at 12 months.
Measured: at 12 months
Progression-free survival (PFS)
PFS is defined as the time from registration until progression according the IMWG criteria or death from any cause, whichever occurs first. Patients not having an event at the time of analysis as well as patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last tumor assessment showing non-progression before starting a new treatment, if any.
Measured: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study start1 Oct 2018
- Primary completion3 Feb 2021
- Study completion3 Feb 2021
Why it stopped: Feasibility (low patient accrual and financial reasons)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thilo Zander, MD, Study chair, Luzerner KantonsspitalChristoph Driessen, Prof, Study chair, Cantonal Hospital of St. GallenChristoph Renner, Prof, Study chair, Onkozentrum Zürich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03520985
- Sponsor's protocol ID
- SAKK 39/16 - OptiPOM
- Acronym
- OptiPOM
- Status last verified
- Jun 2021
- First submitted
- 17 Apr 2018
- Last updated
- 10 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial
- ClinicalTrials.gov ID
- NCT03520985
- Acronym / sponsor ID
- OptiPOM / SAKK 39/16 - OptiPOM
- Conditions
- Refractory Multiple Myeloma
- Keywords
- refractory Multiple Myeloma, Phase II, Pomalidomide, OptiPOM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Feasibility (low patient accrual and financial reasons)
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 3 Feb 2021 (actual)
- Study completion
- 3 Feb 2021 (actual)
- First posted
- 11 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pomalidomide is an approved treatment for refractory multiple myeloma. Toxicity of pomalidomide in the pivotal MM-003 trial, was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule is too toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance. The aim of this trial therefore is to establish that alternate day dosing of pomalidomide (4 mg q2d, d1-28) is non-inferior to daily dosing (4 mg d1-21 q28) in terms of efficacy of the drug with potentially less side effects.
Detailed description
Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all hematological malignancies. Despite recent advances in myeloma treatment, including the introduction of proteasome inhibitors, immunomodulatory drugs (IMiDs) and stem cell transplantation, myeloma remains an incurable disease. The treatment of bortezomib and lenalidomide refractory myeloma is still an unmet medical need. Once patients have relapsed after IMiD-containing therapies and have become bortezomib-resistant, their prognosis is extremely poor.
Pomalidomide is a third-generation, Swissmedic approved, oral immunomodulatory drug with activity in such patients. However the toxicity of pomalidomide in the pivotal MM-003 trial was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule (4 mg daily on 21 of 28 days) is toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance.
Alternative dosing schedules:
There is robust data available indicating that lower pomalidomide doses (e.g. 2 mg daily) lead to similar responses and progression free survival with fewer side effects. Due to its unique pharmacological characteristics, pomalidomide is well suited for alternate day dosing. The decline of the plasma concentration at the terminal phase is slow. These data make pomalidomide an ideal candidate for alternate day dosing. Therefore, a phase I study has already been conducted in 2008 to test the alternating administration of the drug showing excellent responses with a marked reduction of thrombotic events and less severe myelosuppression.
The drug costs of pomalidomide are quite high. Interestingly, the manufacturer determined a pricing model that is independent from the capsule strength (costs for one capsule 1 mg=2 mg=3 mg=4 mg). In patients requiring dose reductions due to hematologic toxicity, daily dosing of reduced strength pomalidomide (e.g. 2 mg daily) is approved and suggested by the manufacturer. This delivers 50% less pomalidomide to the patient, albeit at 100% of the price of full dosing.
In summary, the establishment of the modified pomalidomide schedule would be an interesting option for our patients to achieve similar efficacy with fewer side effects. In addition, it would optimize the cost-effectiveness of the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide | Experimental | Drug: Pomalidomide, Drug: DexamethasoneThe treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient was diagnosed with multiple myeloma based on standard IMWG criteria
- Prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
- Patients must have been exposed to both lenalidomide and bortezomib
- Measurable disease for myeloma defined as one of the following: serum M-protein ≥ 5 g/L; urine M-protein ≥ 0.2 g/24 hours
- Refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy.
Key exclusion criteria (9 listed)
- History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration, with the exception of pT1-2 prostate cancer Gleason score ≤6, adequately treated, cervical carcinoma in situ or localized non-melanoma skin cancer.
- Polyneuropathy grade > 2
- Patients who received any of the following within the last 14 days of initiation of trial treatment:
- Known or clinically suspected myeloma manifestations in the central nervous system
- Severe or uncontrolled cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PomalidomideAlso: Imnovid®Pomalidomide (4 mg p.o.) will be administered on every other day of each 28-day treatment cycle. Treatment duration: Treatment cycles are repeated until confirmed disease progression. | Drug | Pomalidomide |
| DexamethasoneFor patients ≤ 75 years of age: Low-Dose Dexamethasone (40 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle. For patients > 75 years of age: Low-Dose Dexamethasone (20 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle. Treatment duration: Treatment cycles are repeated until confirmed disease progression. | Drug | Pomalidomide |
Primary outcome
Overall Response Rate (ORR)
Time frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
OR is defined as minimal response or better, assessed according to the IMWG criteria.
3 secondary outcomes
Overall Survival (OS)
Time frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
Overall Survival (OS) at 12 months
Time frame: at 12 months
Progression-free survival (PFS)
Time frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months
Results and safety
The study was stopped early (reason given: Feasibility (low patient accrual and financial reasons)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thilo Zander, MD study chair
Luzerner Kantonsspital
Christoph Driessen, Prof study chair
Cantonal Hospital of St. Gallen
Christoph Renner, Prof study chair
Onkozentrum Zürich
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pomalidomide and Dexamethasone in people with Refractory Multiple Myeloma, run by Swiss Cancer Institute at 16 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Feasibility (low patient accrual and financial reasons)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.